Investigation of crosstalk between hedgehog and bone metabolism-related signalings in root resorption

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18467
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Nihon University
• Principal Investigator: KIKUTA Jun 日本大学, 松戸歯学部, 専修医 (10759632)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 歯根吸収 / 歯根膜細胞 / 矯正力 / TGF-βシグナル / Hedgehogシグナル

Outline of Final Research Achievements

In vivo study, rats were subjected to an orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars. In the PDL tissue subjected to the orthodontic force, TGF-β1, SHH, RANKL and IL-6-positive cells were observed.
In vitro study, weights were placed on human periodontal ligament cells (hPDL cells) as the optimal orthodontic force (CF 1g) group and the heavy orthodontic force (CF 4g) group that leads to root resorption. Expression of SHH, RANKL, IL-6 mRNA in the CF4g group were significantly increased compared with the control group. In the CF1g group and CF4g+Hedgehog inhibitor group, the expression of RANKL and IL-6 mRNA was significantly decreased compared with the CF4g group.
The result in this study suggest that orthodontic force induces root resorption via TGF-β signaling and Hedgehog signaling.

Free Research Field

歯科矯正学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、歯根吸収の発生には歯根膜における炎症性サイトカインの発現が関与していること、TGF-βとHedgehogシグナル伝達が炎症性サイトカインの発現を制御していることが明らかとなり、矯正学的歯の移動による歯根吸収の発生について新たな知見が得られた。
また以前の研究結果より、NotchシグナルやWntシグナルなどの骨代謝関連シグナルのクロストークが炎症性サイトカインの発現に関与していることが示唆されており、各シグナルの制御が歯根吸収の抑制に有効であることが証明できれば、将来的に歯根吸収の増悪に対する抑制薬を作製することが期待でき、歯科矯正臨床の今後一層の発展が望めるものとなった。